Atyr Pharma, Inc. · NASDAQ:ATYR
Atyr Pharma — Investor Presentation (August 2017)
33 slides from Atyr Pharma's investor presentation, Aug 28, 2017
Slide 1: Targeting Novel Immune Therapeutic Intervention Points
Targeting Novel Immune Therapeutic Intervention Points First-in-Class Treatments for Patients with Myopathies & Lung Diseases Novel I/O Target for Universal Backbone Therapy for Cancer Patients aTyr Pharma, Inc. August 2017 Exhibit 99.2
Slide 2: Forward-Looking Statements
Forward-Looking Statements The following slides and any accompanying oral presentation contain forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 and other federal securities laws. The use of words such as “may,” “might,” “will,” “should,” “expect,”
Slide 3: LIFE Candidate Pipeline
LIFE Candidate Pipeline All programs currently wholly-owned Resokine Agonist Platform Preclinical Phase 1 Phase 2 Phase 3 Rare Muscular Dystrophies Resolaris Program (ATYR 1940)* Interstitial Lung Diseases iMod.Fc Program (ATYR 1923) Resolaris Program (ATYR 1940) Resokine Antagonist Platform Preclin
Slide 4: Tapping the Power of the Resokine Pathway
Evolved from Cellular Homeostasis Genes over 400 Million Years Tapping the Power of the Resokine Pathway
Slide 5: Resokine Pathway: Evidence For A New Immunological Pathway in Humans
Resokine Pathway: Evidence For A New Immunological Pathway in Humans: Resokine Disrupting the pathway promotes T-cell invasion Homeostasis Imbalance (↑ Immune cell invasion/activity) Diseased Muscle Diseased Lung Healthy muscle Healthy lung 100% (18 of 18) anti-synthetase syndrome patients tested po
Slide 6: Resokine Levels Influence Tolerance and Immunity
Resokine Levels Influence Tolerance and Immunity Resokine pathway as a set point modulator of immune engagement Adapted from graphic from Chen et al 2017 Tolerance Suppression Immunity Inflammation Immune Cell Population n
Slide 7: Resokine Hypothesis in Immune Invaded Tissues
Resokine Hypothesis in Immune Invaded Tissues: Damage Signals Exceed Resokine Ability to Resolve Immune Engagement Adapted from graphic from Chen et al 2017 Tolerance Suppression Immunity Inflammation Immune Cell Population n Muscle Disease Lung Disease
Slide 8: Resokine Hypothesis in Cancer
Resokine Hypothesis in Cancer: Higher than Normal Resokine Adapted from graphic from Chen et al 2017 Tolerance Suppression Immunity Inflammation Immune Cell Population n Tumor Tissue
Slide 9: MOA Hypothesis: T Cells Release Granzyme B
Boivin et al., Lab Invest., 2009 Chen et al., Immunity, 2013 MOA Hypothesis: T Cells Release Granzyme B That Promotes Cell Death & Local Tissue Damage Muscle Disease Lung Disease Tumor Tissue Promotes Cell Death T cell (Activated) T cell (Less Activated) T cell (Activated/ No Resokine) Resokine boun
Slide 10: Resokine Inhibits Granzyme B Release From Activated Human T Cells
Resokine Inhibits Granzyme B Release From Activated Human T Cells Key mediator of T cell cytotoxicity Resokine (pM) Human T Cell Granzyme B Release Post Activation vehicle 30,000 Stimulated Potential For More Tissue Damage **** p < 0.0001 Granzyme B Promotes Cell Death Note: Common with human donors
Slide 11: Resokine Agonists Change T Cell Phenotype
Effector functions at levels closer to a resting T cell Stimulatory pathways at levels closer to a resting T cell Resokine Agonists Change T Cell Phenotype Unique MOA to orchestrate immune homeostasis in activated T cells Shifts trafficking & residence closer to a resting T cell T cell (Less activat
Slide 12: Harnessing New Immunological Insights Across Therapeutic Areas, 3 Modalities
Harnessing New Immunological Insights Across 3 Therapeutic Areas, 3 Therapeutic Modalities TPP = Target Product Profile ILD = Interstitial Lung Disease ORCA = Orchestrating Resokine Complete Antagonism Resolaris “Native Agonist” to Resokine pathway May promote tissue homeostasis in muscle & lung No
Slide 13: Resolaris Program
Harnessing the Resokine Pathway to Treat Multiple Rare Muscle Diseases Resolaris Program
Slide 14: Rare Myopathies Have an Immune Component
Rare Myopathies Have an Immune Component Chronic damage, homeostasis disrupted Genetic Mutation Inappropriate proteins in muscle Mutated dysferlin proteins in muscle Mutated dystrophin proteins in muscle FSHD LGMD2B DMD Aberrant Protein Expression Localized T Cell Invasion/Engagement Untapped therap
Slide 15: Resolaris Program Snapshot
Resolaris Program Snapshot Patients Rare Myopthies with an Immune Component Therapeutic concept Upregulate naturally occurring homeostatic pathway involving immune cells Target Resokine pathway: activated T-cell Rationale Functional knockout in humans & rodents results in increased muscle damage Mol
Slide 16: Resolaris Clinical Data from Three Phase 1/2a Clinical Trials
Resolaris Clinical Data from Three Phase 1/2a Clinical Trials Signals of clinical activity (improved muscle function) in patients n = 4 n = 2 n = 4 n = 8 n = 9 Overall Mean MMT Change Week 14 by Dose Group FSHD & LGMD2B Patients From 002, 003, 004 Trials Mean Change from baseline (%) Decrease Muscle
Slide 17: iMod.Fc Program
Lung Physiocrine Engineered to Treat Multiple Pulmonary Diseases iMod.Fc Program
Slide 18: Interstitial Lung Disease
Interstitial Lung Disease Severe tissue remodeling Resokine Promotes Lung Homeostasis Epithelial damage IL-13, TGFβ, TNF, IL-1β Resokine Therapy to “Cool Down” Immune System Pharmacologic restoration of tissue homeostasis and resolution of immune engagement Natural restoration of tissue homeostasis
Slide 19: Interstitial Lung Diseases Share Immune Engagement
Connective Tissue Diseases (CTDs) Occult CTD + Serologies Idiopathic Pulmonary Fibrosis (IPF) Constant Immune Engagement: Acute & Chronic Sarcoidosis Chronic Hypersensitivity Pneumonia Non-Specific Interstitial Pneumonia Level of Fibrosis Interstitial Lung Diseases Shared Immune Engagement Significa
Slide 20: Pathophysiological Role of T Cells in ILD
Pathophysiological Role of T Cells in ILD Idiopathic Pulmonary Fibrosis Hypersensitivity Pneumonitis Sarcoidosis Prasse et al. Clin Exp Immunol 2000 Daniil et al. Resp Research 2005 Arranz, et al. Eur Resp J 2016 T Cells Correlated with Negative Outcomes Percentage of lymphocytes in pulmonary lavage
Slide 21: iMod.Fc Outperforms Current Treatment
*The Ashcroft scale for the evaluation of bleomycin-induced lung fibrosis is the analysis of stained histological samples by visual assessment **Bleomycin mouse model abstract presented as a poster at the American Thoracic Society in May 2017 Improvement in Ashcroft Score (%)* TGF β Ab 3mg/kg IP QOD
Slide 22: iMod.Fc Returns Breathing to Normal
***P ≤ 0.001; ****P < 0.0001; ns = not significant Respiratory Minute Volume = amount of air inhaled/exhaled/min Nintedanib dosed daily iMod.Fc Returns Breathing to Normal Respiratory Minute Volume iMod.Fc iMod.Fc iMod.Fc outperformed Nintedanib (SOC for IPF) in the respiratory mouse model at lower
Slide 23: iMod.Fc Program Snapshot
iMod.Fc Program Snapshot Patients Interstitial Lung Diseases, including IPF Therapeutic concept Upregulate naturally occurring homeostatic pathway involving immune cells Target Resokine pathway: activated T-cell Rationale Functional knockout in humans & rodents results in lung damage Molecular entit
Slide 24: iMod.Fc Phase 1/2a Program Current Plan
Phase 2a Potential Patient Analysis: BALF Imaging: HRCT, PET Disease Biomarkers: ACE, IL-2R, Neopterin, Resokine PD Assay iMod.Fc Phase 1/2a Program Current Plan Program Overview (Final trial designs subject to approval of regulatory authorities) Randomized, Double-Blind, Placebo-Controlled Studies
Slide 25: Resokine Cancer: Promoting Tumor Homeostasis
By Hijacking a 400 Million Year Old Pathway, Resokine Cancer Promoting Tumor Homeostasis
Slide 26: Resokine: Potential Key Regulator of Tissue & Tumor Homeostasis
Resokine: Potential Key Regulator of Tissue & Tumor Homeostasis Cancer homeostasis follows homeostasis evolution tRNA Synthetase Physiocrines *Resokine, CTLA-4, PD-1 timeline for when >70% sequence identity Guo et al. Nature 2010; Science 2017; Science 2007; Nature 2002; Nature 2010; Genome Research
Slide 27: Project ORCA: Resokine Antagonists
B Project ORCA: Resokine Antagonists Activating T Cells “Turning Up the Heat” To Disrupt Tumor Homeostasis
Slide 28: Higher Resokine Levels in Tumors: Colder Immune System
Higher Resokine Levels in Tumors: Colder Immune System at the Tumor Adapted from graphic from Chen et al 2017 Tolerance Suppression Immunity Inflammation Immune Cell Population n 2 Increases the local tumor requirement for immune cell activation/ engagement 1 Tumor “highjacks” the primal homeostatic
Slide 29: Setting Lower Resokine Levels in Cancer Patients
Setting Lower Resokine Levels in Cancer Patients in Tumors: Hotter Immune System at the Tumor Adapted from graphic from Chen et al 2017 Tolerance Suppression Immunity Inflammation Immune Cell Population n 1 Potential to therapeutically disrupt cancer homeostasis 2 Target Resokine Pathway 3 With an a
Slide 30: ORCA: Development Highlights & Status
ORCA: Development Highlights & Status Development Highlights Status Resokine over expressed in all cancers tested to date Over 10 tumor types tested; >300 patient samples tested; ≥95% of patients tested positive for Resokine Human evidence of Ab blockade; changes T cell behavior Anti-synthetase synd
Slide 31: Building a New Class of Therapeutics For Patients
Building a New Class of Therapeutics For Patients Foundation for the Future
Slide 32: LIFE Leaders
LIFE Leaders Andrea Cubitt, Ph.D. VP, Product Protection John Blake, CPA SVP, Finance Sanjay Shukla, M.D. Chief Medical Officer Holly D. Chrzanowski VP, Enterprise Talent and Organization Ashraf Amanullah, Ph.D. VP, Manufacturing John Mendlein, Ph.D. Chief Executive Officer Sanuj Ravindran, M.D. Chi
Slide 33: LIFE Corporate Goals and Financial Update
LIFE Corporate Goals and Financial Update Corporate Goals Advance Pipeline with Two Molecules in the Clinic iMod.Fc scheduled to commence Phase 1 in 2017 Declare 3rd IND Candidate ORCA on track to declare an IND candidate in 2017 Partner One or More Wholly-Owned Programs Active discussions ongoing (